Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer

BACKGROUND: Identifying predictors of treatment toxicity and overall survival (OS) is important for selecting patients who will benefit from chemotherapy. In younger patients with cancer, muscle mass and radiodensity are associated with treatment toxicity and OS. In this study, we investigated whether muscle mass, radiodensity, and strength were associated with treatment toxicity and OS in patients with advanced cancer aged 60 years or older. MATERIALS AND METHODS: Before starting palliative chemotherapy, muscle mass and radiodensity were assessed using computed tomography scans and muscle strength was assessed using a hydraulic hand grip dynamometer. Treatment toxicity was defined as any toxicity resulting in dose reduction and/or discontinuation of treatment. Multiple logistic and Cox regression analyses were performed to study potential associations of muscle mass, radiodensity, and strength with treatment toxicity and OS, respectively. RESULTS: The participants were 103 patients, with a mean age of 70 years, with advanced colorectal, prostate, or breast cancer. Muscle parameters were not significantly associated with treatment toxicity. Higher muscle strength was associated with longer OS (hazard ratio 1.03; 95% confidence interval 1.00-1.05). Muscle mass and radiodensity were not significantly associated with OS. CONCLUSION: Higher muscle strength at the start of palliative chemotherapy is associated with significantly better OS in older patients with advanced cancer. None of the investigated muscle parameters were related to treatment toxicity. Future studies are needed to evaluate whether muscle strength can be used for treatment decisions in older patients with advanced cancer. IMPLICATIONS FOR PRACTICE: This study in older patients with advanced cancer showed that adequate muscle strength is associated with longer overall survival. The results of this study imply that muscle strength might be helpful in estimating survival and therefore in identifying older patients who will benefit from anticancer treatment

Increase in the prevalence of mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso.

BACKGROUND: Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy (IPTp-SP) is widely implemented to prevent these negative effects of malaria. However, resistance against SP by P. falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P. falciparum are associated with SP resistance. In this study the prevalence of SP resistance mutations was determined among P. falciparum found in pregnant women and the general population (GP) from Nanoro, Burkina Faso and the association of IPTp-SP dosing and other variables with mutations was studied. METHODS: Blood spots on filter papers were collected from pregnant women at their first antenatal care visit (ANC booking) and at delivery, from an ongoing trial and from the GP in a cross-sectional survey. The dhps and dhfr genes were amplified by nested PCR and products were sequenced to identify mutations conferring resistance (ANC booking, n = 400; delivery, n = 223; GP, n = 400). Prevalence was estimated with generalized estimating equations and for multivariate analyses mixed effects logistic regression was used. RESULTS: The prevalence of the triple dhfr mutation was high, and significantly higher in the GP and at delivery than at ANC booking, but it did not affect birth weight. Furthermore, quintuple mutations (triple dhfr and double dhps mutations) were found for the first time in Burkina Faso. IPTp-SP did not significantly affect the occurrence of any of the mutations, but high transmission season was associated with increased mutation prevalence in delivery samples. It is unclear why the prevalence of mutations was higher in the GP than in pregnant women at ANC booking. CONCLUSION: The high number of mutants and the presence of quintuple mutants in Burkina Faso confirm concerns about the efficacy of IPTp-SP in the near future. Other drug combinations to tackle malaria in pregnancy should, therefore, be explored. An increase in mutation prevalence due to IPTp-SP dosing could not be confirmed

Controlled evaluation of a transition clinic for Dutch young people with cystic fibrosis

Background: Transition clinics (TCs) are advocated as best practice to support young people with cystic fibrosis (CF) during transition to adulthood and adult care. We aimed to research the functioning of a TC for young people with CF compared with direct hand-over care and to evaluate whether those treated at the TC have better transfer experiences and outcomes compared with the control group. Methods: Mixed-methods retrospective controlled design, including interviews with professionals, observations of clinics, chart reviews (at four measurement moments), and patient surveys. Qualitative data analysis focused on organization and daily routines, and barriers and facilitators experienced. Young people's transfer experiences, self-management, health care use, and clinical outcomes were assessed quantitatively. Results: The most notable feature distinguishing the TC and direct hand-over care comprised joint consultations between pediatric and adult care professionals in the former. A transition coordinator was considered essential for the success of the TC. The main barriers were lack of time, planning, and reimbursement issues. Young people treated at the TC tended to have better transfer experiences and were more satisfied. They reported significantly more trust in their adult care professionals. Their self-management-related outcomes were less favorable. Conclusions: The TC had several perceived benefits and showed positive trends in transfer experiences and satisfaction, but no differences in health-related outcomes. Structured preparation of young people, joint consultations with pediatric and adult care professionals, and better coordination were perceived as facilitating elements. Further improvement demands solutions for organizational and financial barriers, and better embedding of self-management interventions in CF care

A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya

<p>Abstract</p> <p>Background</p> <p>Many countries have implemented artemisinin-based combination therapy (ACT) for the first-line treatment of malaria. Although many studies have been performed on efficacy and tolerability of the combination arthemeter-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP), less is known of the effect of these drugs on gametocyte development, which is an important issue in malaria control.</p> <p>Methods and results</p> <p>In this two-arm randomized controlled trial, 146 children were treated with either AL or DP. Both groups received directly observed therapy and were followed for 28 days after treatment. Blood samples were analysed with microscopy and NASBA. In comparison with microscopy NASBA detected much more gametocyte positive individuals. Moreover, NASBA showed a significant difference in gametocyte clearance in favour of AL compared to DP. The decline of parasitaemia was slower and persistence or development of gametocytes was significantly higher and longer at day 3, 7 and 14 in the DP group but after 28 days no difference could be observed between both treatment arms.</p> <p>Conclusion</p> <p>Although practical considerations could favour the use of one drug over another, the effect on gametocytogenesis should also be taken into account and studied further using molecular tools like NASBA. This also applies when a new drug is introduced.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN36463274</p

DataSheet_1_Development of a standardized and validated flow cytometry approach for monitoring of innate myeloid immune cells in human blood.zip

Innate myeloid cell (IMC) populations form an essential part of innate immunity. Flow cytometric (FCM) monitoring of IMCs in peripheral blood (PB) has great clinical potential for disease monitoring due to their role in maintenance of tissue homeostasis and ability to sense micro-environmental changes, such as inflammatory processes and tissue damage. However, the lack of standardized and validated approaches has hampered broad clinical implementation. For accurate identification and separation of IMC populations, 62 antibodies against 44 different proteins were evaluated. In multiple rounds of EuroFlow-based design-testing-evaluation-redesign, finally 16 antibodies were selected for their non-redundancy and separation power. Accordingly, two antibody combinations were designed for fast, sensitive, and reproducible FCM monitoring of IMC populations in PB in clinical settings (11-color; 13 antibodies) and translational research (14-color; 16 antibodies). Performance of pre-analytical and analytical variables among different instruments, together with optimized post-analytical data analysis and reference values were assessed. Overall, 265 blood samples were used for design and validation of the antibody combinations and in vitro functional assays, as well as for assessing the impact of sample preparation procedures and conditions. The two (11- and 14-color) antibody combinations allowed for robust and sensitive detection of 19 and 23 IMC populations, respectively. Highly reproducible identification and enumeration of IMC populations was achieved, independently of anticoagulant, type of FCM instrument and center, particularly when database/software-guided automated (vs. manual “expert-based”) gating was used. Whereas no significant changes were observed in identification of IMC populations for up to 24h delayed sample processing, a significant impact was observed in their absolute counts after >12h delay. Therefore, accurate identification and quantitation of IMC populations requires sample processing on the same day. Significantly different counts were observed in PB for multiple IMC populations according to age and sex. Consequently, PB samples from 116 healthy donors (8-69 years) were used for collecting age and sex related reference values for all IMC populations. In summary, the two antibody combinations and FCM approach allow for rapid, standardized, automated and reproducible identification of 19 and 23 IMC populations in PB, suited for monitoring of innate immune responses in clinical and translational research settings.Peer reviewe

Systematic Review into Diagnostics for Post-Kala-Azar Dermal Leishmaniasis (PKDL)

Identification of post-kala-azar dermal leishmaniasis (PKDL) is important due to the long and toxic treatment and the fact that PKDL patients may serve as a reservoir for visceral leishmaniasis (VL). We summarized the published literature about the accuracy of diagnostic tests for PKDL. We searched Medline for eligible studies investigating the diagnostic accuracy of any test for PKDL. Study quality was assessed using QUADAS-2. Data were extracted from 21 articles including 43 separate studies. Twenty-seven studies evaluated serological tests (rK39 dipstick, ELISA, DAT, and leishmanin tests), six studies molecular tests, eight microscopy, and two cultures. Only a few of these studies reported a valid estimate of diagnostic accuracy, as most were case-control designs or used a reference standard with low sensitivity. The included studies were very heterogeneous, for example, due to a large variety of reference standards used. Hence, no summary estimates of sensitivity or specificity could be made. We recommend well-designed diagnostic accuracy trials that evaluate, side-by-side, all currently available diagnostics, including clinical symptoms, serological, antigen, molecular, and parasitological tests and possible use of statistical modelling to evaluate diagnostics when there is no suitable gold standar

New developments in malaria diagnostics Monoclonal antibodies against Plasmodium dihydrofolate reductase-thymidylate synthase, heme detoxification protein and glutamate rich protein

Currently available rapid diagnostic tests (RDTs) for malaria show large variation in sensitivity and specificity, and there are concerns about their stability under field conditions. To improve current RDTs, monoclonal antibodies (mAbs) for novel malaria antigens have been developed and screened for their possible use in new diagnostic tests. Three antigens, glutamate rich protein (GLURP),dihydrofolate reductase-thymidylate synthase (DHFR-TS) and heme detoxification protein (HDP), were selected based on literature searches. Recombinant antigens were produced and used to immunize mice. Antibody-producing cell lines were subsequently selected and the resulting antibodies were screened for specificity against Plasmodium falciparum and Plasmodium vivax. The most optimal antibody couples were selected based on antibody affinity (expressed as dissociation constants, K-D) and detection limit of crude antigen extract from P. falciparum 3D7 culture. The highest affinity antibodies have K-D values of 0.10 nM +/- 0.014 (D5) and 0.068 +/- 0.015 nM (D6) for DHFR-TS mAbs, 0.10 +/- 0.022 nM (H16) and 0.21 +/- 0.022 nM (H18) for HDP mAbs and 0.11 +/- 0.028 nM (G23) and 0.33 +/- 0.093 nM (G22) for GLURP mAbs. The newly developed antibodies performed at least as well as commercially available histidine rich protein antibodies (K-D of 0.16 +/- 0.13 nM for PTL3 and 1.0 +/- 0.049 nM for C1-13), making them promising reagents for further test developmen

Risk Factors of Coxiella burnetii (Q Fever) Seropositivity in Veterinary Medicine Students

Background: Q fever is an occupational risk for veterinarians, however little is known about the risk for veterinary medicine students. This study aimed to assess the seroprevalence of Coxiella burnetii among veterinary medicine students and to identify associated risk factors. Methods: A cross-sectional study with questionnaire and blood sample collection was performed among all veterinary medicine students studying in the Netherlands in 2006. Serum samples (n = 674), representative of all study years and study directions, were analyzed for C. burnetii IgG and IgM phase I and II antibodies with an immunofluorescence assay (IFA). Seropositivity was defined as IgG phase I and/or II titer of 1:32 and above. Results: Of the veterinary medicine students 126 (18.7%) had IgG antibodies against C. burnetii. Seropositivity associated risk factors identified were the study direction ‘farm animals ’ (Odds Ratio (OR) 3.27 [95 % CI 2.14–5.02]), advanced year of study (OR year 6: 2.31 [1.22–4.39] OR year 3–5 1.83 [1.07–3.10]) having had a zoonosis during the study (OR 1.74 [1.07–2.82]) and ever lived on a ruminant farm (OR 2.73 [1.59–4.67]). Stratified analysis revealed study direction ‘farm animals ’ to be a studyrelated risk factor apart from ever living on a farm. In addition we identified a clear dose-response relation for the number of years lived on a farm with C. burnetii seropositivity. Conclusions: C. burnetii seroprevalence is considerable among veterinary medicine students and study related risk factor

Antigen persistence of rapid diagnostic tests in pregnant women in Nanoro, Burkina Faso, and the implications for the diagnosis of malaria in pregnancy

Objectives To evaluate persistence of several Plasmodium antigens in pregnant women after treatment and compare diagnostics during treatment follow-up. methods Thirty-two pregnant women (N = 32) with confirmed malaria infection by a histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) and microscopy were followed for 28 days after artemisinin-based combination therapy (ACT). A Plasmodium lactate dehydrogenase (pLDH)-based RDT and two ELISAs based on the detection of dihydrofolate reductase-thymidylate synthase (DHFRTS) and haeme detoxification protein (HDP) were compared with each other and to RT-PCR at each visit. results The mean visit number (95% confidence interval) on which the HRP2-based RDT was still positive after treatment was 3.4 (2.7-4.1) visits with some patients still positive at day 28. This is significantly later than the pLDH-based RDT [0.84 (0.55-1.1)], microscopy (median 1, range 1-3), DHFR-TS-ELISA [1.7 (1.1-2.3)] and RT-PCR (median 2, range 1-5) (P <0.05), but not significantly later than HDP-ELISA [2.1 (1.6-2.7)]. Lower gravidity and higher parasite density at day 0 resulted in significantly longer positive results with most tests (P <0.05). conclusions HRP2 can persist up to 28 days after ACT treatment; therefore, this test is not suitable for treatment follow-up in pregnant women and can generate problems when using this test during intermittent preventive treatment (IPTp). DHFR-TS is less persistent than HRP2, making it a potentially interesting target for diagnosi